scholarly journals Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somatostatin analogues: PAPE extension study

2018 ◽  
Vol 179 (5) ◽  
pp. 269-277 ◽  
Author(s):  
Ammar Muhammad ◽  
Eva C Coopmans ◽  
Patric J D Delhanty ◽  
Alof H G Dallenga ◽  
Iain K Haitsma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Somatostatin Analogues ◽  
Tolerance Test ◽  
Extension Study ◽  
Oral Glucose ◽  
Efficacy And Safety ◽  
Igf I ◽  
Core Study ◽  
Long Acting

ObjectiveTo assess the efficacy and safety after 48 weeks of treatment with pasireotide long-acting-release (PAS-LAR) alone or in combination with pegvisomant in patients with acromegaly. In addition, we assessed the relation between insulin secretion and pasireotide-induced hyperglycemia.DesignThe PAPE extension study is a prospective follow-up study until 48 weeks after the core study of 24 weeks.MethodsFifty-nine out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (≤1.2× the upper limit of normal (ULN)) at 48 weeks through protocol-based adjustment of pegvisomant and PAS-LAR doses. At baseline, insulin secretion was assessed by an oral glucose tolerance test (OGTT).ResultsAt the end of the study, median IGF-I was 0.98× ULN, and 77% of patients achieved normal IGF-I levels with a mean pegvisomant dose of 64 mg/week, and an overall cumulative pegvisomant dose reduction of 52%. Frequency of diabetes mellitus increased from 68% at 24 weeks to 77% at 48 weeks, and nine patients discontinued PAS-LAR treatment, mainly because of severe hyperglycemia. Pasireotide-induced hyperglycemia was inversely correlated with baseline insulin secretion (r = −0.37,P < 0.005).ConclusionsPAS-LAR normalizes IGF-I levels in most acromegaly patients, with a 50% pegvisomant-sparing effect. However, PAS-LAR treatment coincided with a high incidence of diabetes mellitus. The risk for developing diabetes during PAS-LAR treatment seems inversely related to insulin secretion at baseline.

scholarly journals Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA)

2004 ◽  
pp. 439-446 ◽  
Author(s):  
A Mestron ◽  
SM Webb ◽  
R Astorga ◽  
P Benito ◽  
M Catala ◽  
...  
Keyword(s):  
Visual Fields ◽  
Somatostatin Analogues ◽  
Tolerance Test ◽  
Sleep Apnoea ◽  
Morbidity And Mortality ◽  
Oral Glucose ◽  
Cancer Breast ◽  
Initial Symptoms ◽  
Igf I ◽  
Epidemiological Characteristics

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.

scholarly journals Incretin hypersecretion in gestational diabetes mellitus

2021 ◽  
Author(s):  
Louise Fritsche ◽  
Martin Heni ◽  
Sabine S. Eckstein ◽  
Julia Hummel ◽  
Annette Schuermann ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Birth Weight ◽  
Gestational Diabetes ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Compensatory Mechanism ◽  
Oral Glucose Tolerance ◽  
Gestational Week

Background Incretins are crucial stimulators of insulin secretion after food intake. We investigated the incretin response during an oral glucose tolerance test in pregnant women with and without gestational diabetes. Methods Subjects underwent a 5-point OGTT with 75 g glucose. We assessed insulin secretion and levels of total GLP-1, GIP, glicentin and glucagon during the OGTT. Findings We examined 167 women (33 with GDM) during gestational week 26.95 (2.15 SD). Insulin secretion was significantly lower in women with GDM (p<0.001). Postprandial GLP-1 and GIP were ~20% higher in women with GDM (all p<0.05) independent from age, BMI and gestational age. GLP-1 increase associated with insulin secretion only in GDM, but not in NGT. Postprandial GLP-1 levels associated negatively with birth weight. Interpretation The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.

scholarly journals Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins

2018 ◽  
Vol 178 (2) ◽  
pp. 153-161 ◽  
Author(s):  
Rikke Beck Jensen ◽  
Ajay Thankamony ◽  
Klaus K Holst ◽  
Joseph A M J L Janssen ◽  
Anders Juul ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Negative Relationship ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Entire Cohort ◽  
Igf I ◽  
Heritability Estimates ◽  
Igfbp 3

Objective IGF-I may be a marker of later metabolic and cardiovascular disease. The interactions between IGF-I and glucose metabolism are multifactorial, and there is potential confounding from several secondary effects. In this study, we examined the interaction between IGF-I and glucose metabolism in a large cohort of clinically well-characterized elderly twins. Design A total of 303 twin pairs of the same gender (606 twins) were included in the study; 125 monozygotic and 178 dizygotic twin pairs. Methods A clinical examination including a standard oral glucose tolerance test (OGTT) and anthropometric measurements was performed. Results The heritability estimates were high for IGF-I and IGFBP-3 (h2: 0.65 (95% CI: 0.55–0.74) and 0.71 (0.48–0.94), respectively) and for insulin secretion (h2 = 0.56, P < 0.0001), whereas the heritability estimates for insulin sensitivity were low (h2 = 0.14, P = 0.11). In a multiple regression analysis (adjusting for age, gender and twin status), there was a negative association between IGF-I and insulin sensitivity (B: −0.13, SE 0.03, P < 0.0001) and IGF-I and disposition index (B: −0.05, SE 0.02, P < 0.001) in the entire cohort of 606 twins. The associations between IGF-I and both DI and HOMA-S did not differ between the DZ and MZ twins. Forty-five twin pairs were discordant for T2D, but the discordant twins had similar concentrations of IGF-I or IGFBP-3. Conclusions There was a high heritability for IGF-I and IGFBP-3, but a low heritability for insulin secretion and insulin sensitivity in a group of elderly twins. In addition, we found a strong negative relationship between IGF-I and insulin sensitivity, which did not seem to be strongly genetically determined.

Cinammon (Cinnamomum Spp.) and Type 2 Diabetes Mellitus

2019 ◽  
Vol 18 (3) ◽  
pp. 247-255
Author(s):  
Sierra-Puente D. ◽  
Abadi-Alfie S. ◽  
Arakanchi-Altaled K. ◽  
Bogard-Brondo M. ◽  
García-Lascurain M. ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Key Aspects

Spices such as cinnamon (Cinnamomum Spp.) have been of interest due to their phytochemical composition that exert hypoglycemic effects with potential for management of type 2 diabetes mellitus (T2DM). We summarize data from 27 manuscripts that include, one book chapter, 3 review articles, 10 randomized controlled trials, 4 systematic reviews with meta-analysis, and 9 preclinical studies. The most frequently used cinnamon variety was Cinnamomum cassia rather than the Cinnamomum zeylanicum, whereas outcomes were defined as fasting blood glucose, glycated hemoglobin, and oral glucose tolerance test. A great variability in methodology such as different doses (from 120 mg to 6 g), duration of intervention, data retrieved and use of different concomitant medication, were found to be key aspects of most of trials and systematic reviews with meta-analysis available to date. Low quality studies have been made in most cases with a lot of heterogeneity clouding significance of results. More research needs to be done in order to yield accurate evidence for evidence-based recommendations. Its use is not currently a reliable nor advisable option for the treatment of T2DM.

The Association between Maternal/Fetal Insulin Receptor Substrate 1 Gene Polymorphism rs1801278 and Gestational Diabetes Mellitus in a Chinese Population

2021 ◽  
pp. 1-8
Author(s):  
Lingling Wu ◽  
Changping Fang ◽  
Jun Zhang ◽  
Yanchou Ye ◽  
Haiyan Zhao
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gene Polymorphism ◽  
Gestational Diabetes Mellitus ◽  
Insulin Receptor ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Insulin Receptor Substrate ◽  
Single Center ◽  
Insulin Receptor Substrate 1

<b><i>Objectives:</i></b> Insulin receptor substrate 1 (IRS1) is a crucial factor in the insulin signaling pathway. IRS1 gene polymorphism rs1801278 in mothers has been reported to be associated with gestational diabetes mellitus (GDM). However, it is not clear whether IRS1 gene polymorphism rs1801278 in fetuses is associated with their mothers’ GDM morbidity. The purpose of this study is to analyze the association between maternal, fetal, or maternal/fetal <i>IRS1</i> gene polymorphism rs1801278 and GDM risk. <b><i>Design:</i></b> The study was a single-center, prospective cohort study. In total, 213 pairs of GDM mothers/fetuses and 191 pairs of control mothers/fetuses were included in this study. They were recruited after they underwent oral glucose tolerance test during 24–28 weeks of gestation and followed up until delivery. All participants received the conventional interventions (diet and exercise), and no special therapy except routine treatment. <b><i>Methods:</i></b> A total of 213 pairs of GDM mothers/fetuses and 191 pairs of normal blood glucose pregnant mothers/fetuses were ge­notyped using PCR and DNA sequencing from January 2015 to September 2016. Maternal/fetal <i>IRS1</i> gene polymorphism rs1801278 was analyzed and compared between 2 groups. <b><i>Results:</i></b> There were no significant differences in the frequency of individual mothers’ or fetuses’ <i>IRS1</i> rs1801278 polymorphisms between 2 groups; if both the mothers and fetuses carried A allele, significantly lower GDM morbidity was observed in the mothers. <b><i>Limitations:</i></b> The sample size was relatively small as a single-center study. <b><i>Conclusions:</i></b> Our study suggested that maternal/fetal rs1801278 polymorphism of <i>IRS1</i> is a modulating factor in GDM; both mothers/fetuses carrying the A allele of rs1801278 may protect the mothers against the development of GDM.

scholarly journals Incidence of diabetes mellitus and associated risk factors in the adult population of the Basque country, Spain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Inés Urrutia ◽  
◽  
Alicia Martín-Nieto ◽  
Rosa Martínez ◽  
J Oriol Casanovas-Marsal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Family History ◽  
Basque Country ◽  
Adult Population ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Family History Of Diabetes ◽  
History Of ◽  
Incident Cases

AbstractThe aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11–9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846–0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.

scholarly journals Breastfeeding Duration and Development of Dysglycemia in Women Who Had Gestational Diabetes Mellitus: Evidence from the GUSTO Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 408
Author(s):  
Sumali S. Hewage ◽  
Xin Yu Hazel Koh ◽  
Shu E. Soh ◽  
Wei Wei Pang ◽  
Doris Fok ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Tolerance Test ◽  
Diabetes Risk ◽  
Breastfeeding Duration ◽  
Oral Glucose ◽  
Inverse Association ◽  
Index Pregnancy

(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study (n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.

scholarly journals Cotreatment with Pegvisomant and a Somatostatin Analog (SA) in SA-Responsive Acromegalic Patients

2011 ◽  
Vol 96 (8) ◽  
pp. 2405-2413 ◽  
Author(s):  
Michael Madsen ◽  
Per L. Poulsen ◽  
Hans Ørskov ◽  
Niels Møller ◽  
Jens O. L. Jørgensen
Keyword(s):  
Glucose Tolerance ◽  
Low Dose ◽  
Tolerance Test ◽  
Somatostatin Analog ◽  
Oral Glucose ◽  
Tertiary Referral Center ◽  
Elevated Liver Enzymes ◽  
Igf I ◽  
Insufficient Response

Abstract Context: Cotreatment of acromegaly with pegvisomant and a somatostatin analog (SA) has proven feasible. Previous studies in the field have focused on patients with an insufficient response to SA monotherapy in whom pegvisomant was added without changing the SA dose. Objective: The objective of the study was to study whether patients sufficiently controlled on SA monotherapy can be transferred to combination therapy with low-dose pegvisomant and a reduced SA dose. Design: Eighteen acromegalic patients well controlled on SA monotherapy, mean ± se aged 54 ± 3 yr, were randomized in a parallel study over 24 wk to unchanged SA monotherapy or cotreatment with pegvisomant (15–30 mg twice a week) and SA (half the usual dosage). Setting: This was an investigator-initiated study in a single tertiary referral center. Main Outcome Measures: Glucose tolerance, substrate metabolism, insulin sensitivity, body composition, and quality of life were measured. Results: Median pegvisomant dose was 52.5 mg/wk (range 30–60). IGF-I (micrograms per liter) was comparable both at baseline (P = 0.88) and after 24 wk of treatment (P = 0.48). The change in IGF-I between baseline and wk 24 also did not differ between groups (P = 0.15). Apart from increased peak insulin levels during the oral glucose tolerance test in the cotreatment group, no substantial differences between the two groups were detected. Moderately elevated liver enzymes were found in 17% of the patients on pegvisomant therapy. Conclusion: Acromegalic patients well controlled on SA monotherapy can maintain safe IGF-I levels during 24 wk of cotreatment with low-dose pegvisomant and a 50% reduced SA dose. This treatment modality, however, does not seem to provide significant benefits for the patients.

Sign in / Sign up

Export Citation Format

Share Document